Environmental and genetic factors are believed to contribute to Neurodegenerative disorders such as Amyotrophic Lateral Sclerosis, Parkinson's, Huntington and Alzheimer's diseases. In general, these diseases are poorly understood at the molecular and biochemical levels with no effective therapies. A better understanding of environmental triggers that influence disease development and the interplay between these exposures and a person's underlying genetic susceptibility will result in earlier detection, better understanding of disease mechanisms, and ultimately the design of prevention strategies. Metabolomics is a powerful new technology platform for the comprehensive study of the metabolome, the repertoire of bio-chemicals (or small molecules) present in cells, tissue and body fluid. It can provide signatures for disease states in ways not possible before and maps these changes to aberrent biochemical pathways. Environmental insults and genetic mutations leave long lasting changes in the metabolome that can be captured in modified signatures. In the proposed studies we will extend our current observations of biochemical abnormalities (signatures) in the sera of ALS patients, both familial and sporadic, but using the new chemically capable metabolomic platform. We will confirm the specificity of these signatures by comparing them to signatures from patients with general neuropathies, myopathies and other neurodegenerative diseases. Specific aims for Phase I: 1. Collect clinical data and plasma samples from subjects with ALS and disease and non-disease comparison groups. 2. Begin to identify unique metabolomic profiles for sporadic ALS (SALS) and familial ALS (FALS) by comparing to those from patients with peripheral nervous system disorders, other neurodegenerative disorders and healthy controls. In Phase II we will propose to develop diagnostic and surrogate marker products for ALS. Long-term goals are to use metabolomics as a powerful tool to map environmental factors that contribute to the development of neurodegnerative diseases. [unreadable] [unreadable] [unreadable]